Idiopathic osteoporosis is a disease of unknown etiology characterized by progressive loss of bone mass and increased fragility, resulting in a marked increase in susceptibility to fractures. Osteoporosis is among the most prevalent of all musculoskeletal disorders, afflicting fifty-six percent of women over 45 years of age. Praemer et al., Musculoskeletal Conditions in the United States, American Academy of Orthopaedic Surgeons, Park Ridge, Ill. (1992). Because its incidence increases with age and the percentage of elderly in the population is increasing, osteoporosis will become more common with time. Osteoporosis is difficult to treat locally, and there is presently no known cure. Finally, and most significantly, osteoporosis is associated with a substantial morbidity and mortality. The most serious fracture resulting from osteoporosis is that of the proximal femur in the region of the hip joint. With an annual incidence of over 300,000, hip fractures are currently the most common fracture in the elderly. One out of every six Caucasian women will have a hip fracture during her lifetime (Cummings et al., Arch Intern Med 149:2455-2458 (1989)), and for those who attain the age of 90, this figure becomes one in three.
Of the patients who are independent and living at home at the time of hip fracture, approximately 20 percent remain in a long term care institution for at least one year following the fracture. During the first year following injury, the mortality rate is approximately 15% higher than for age and gender matched controls. Praemer et al., supra. The increased incidence of proximal femur fracture observed in elderly patients is mainly related to a decreased bone density of their proximal femora, as well as an increased propensity to fall. There is an inverse relationship between the age-related bone loss in the proximal femur and the risk of hip fracture. Each decrease of one standard deviation (SD) in femoral neck bone density increases the age-adjusted risk of hip fracture 2.6 times (95% Cl 1.9-3.6), and women with bone density in the lowest quartile have an 8.5-fold greater risk of hip fracture than those in the highest quartile. Cummings et al., The Lancet 341:72-75 (1993). This relation between hip bone mass and hip fracture risk allows the screening and identification of patients at risk for fracture. Patients who are two standard deviations below peak hip bone mass have passed beneath the “fracture threshold.”
Current therapies for osteoporosis are systemic. These include fluoride, bisphosphonates, calcitonin, estrogens and progestins, testosterone, vitamin D metabolites, and/or calcium. In the United States, only estrogens and alendronate, a bisphosphonate, are indicated for the prevention of hip fractures in postmenopausal osteoporotic women. Each of these agents requires continuous administration over a time period of years.
In addition to treating osteoporotic bone, a need exists for methods of treating or preventing osteoporosis-related fractures, for example by local administration of osteogenic proteins. Because of this need, despite the variety and availability of carrier materials for delivering osteogenic proteins, a need also exists for safe, effective and generally applicable carriers for local treatment of bone defects. Accordingly, despite substantial endeavors in this field, there remains a need for an effective method of repair and/or treatment of osteoporotic and osteopenic bone, and for minimizing or reducing the incidence or severity of osteoporosis-related fractures.